Is APOL5 p.Phe102Cys (c.305T>G) pathogenic?

APOL5 p.Phe102Cys (c.305T>G) is classified Uncertain significance in APOL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: ambiguous (0.5266); Very rare (popmax 8.47e-05%, nfe).

How common is APOL5 p.Phe102Cys (c.305T>G) in the general population?

APOL5 p.Phe102Cys (c.305T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about APOL5 p.Phe102Cys (c.305T>G)?

AlphaMissense predicts ambiguous (score 0.5266) — an in-silico prediction, not a clinical call.

APOL5 p.Phe102Cys

c.305T>G · rs1230323364 · VCV3128044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5266	ambiguous · top 4% in APOL5
REVEL	0.227	benign-leaning
SaProt	LLR -9.28	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	GERP 0.099, phastCons 0.01
Regional constraint	o/e 1.00	unconstrained · MANE · 8,840 bp · p 0.97 · regional, not allelic
Overall
CADD	18.95	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 0.000137% 2/1,461,800 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	8.47e-05%	1,180,040

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APOL5
Protein: p.Phe102Cys
Coding: c.305T>G
MANE Select: NM_030642
dbSNP: rs1230323364
Type: single nucleotide variant
Location: chr22:35726373 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 41.66

Full APOL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOL5 p.Glu81Lys Benign ★★ same type
APOL5 p.Ala124Glu Uncertain significance ★ ⚠ same type
APOL5 p.Ala141Asp Uncertain significance ★ ⚠ same type
APOL5 p.Ala146Asp Uncertain significance ★ ⚠ same type
APOL5 p.Ala163Glu Uncertain significance ★ ⚠ same type
APOL5 p.Ala197Ser Uncertain significance ★ ⚠ same type
APOL5 p.Ala198Gly Uncertain significance ★ ⚠ same type
APOL5 p.Ala226Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/apol5-p-phe102cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown